tbuckley/cabot-search huggingface dataset:
IMerge: Results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA).
Authors: Amer Methqal Zeidan, Uwe Platzbecker, Valeria Santini, Pierre Fenaux, Mikkael A. Sekeres, Michael R. Savona, Yazan F. Madanat, Maria Diez-Campelo, David Valcarcel, Thomas Illmer, Anna Jonasova, Petra Belohlavkova, Laurie Jill Sherman, Tymara Berry, Souria Dougherty, Sheetal Shah, Libo Sun, Ying Wan, Fei Huang, Rami S. Komrokji
Journal: Journal of Clinical Oncology (2023)

7004 Background: Unmet needs remain for red blood cell (RBC) TD pts with LR-MDS R/R or ineligible for ESA. In P2 of the IMerge study (NCT02598661), heavily RBC TD ESA R/R non-del(5q) LR-MDS pts naive to lenalidomide and hypomethylating agents (len/HMA) treated with imetelstat, a telomerase inhibitor, achieved durable and continuous transfusion independence (TI). We report primary data from the P3 study of imetelstat in such pts. Methods: Heavily RBC TD ESA R/R non-del(5q) LR-MDS pts naive to len/HMAs were randomized 2:1 to receive imetelstat 7.5 mg/kg or placebo every 4 wks. Primary endpoint was 8-wk TI; subgroup analyses included IPSS risk, prior transfusion burden and ring sideroblast (RS) status. Secondary endpoints included 24-wk TI, TI duration and hematologic improvement-erythroid (HI-E). Variant allele frequency (VAF) changes were explored. Results: As of Oct 2022, 178 pts were randomized. The primary endpoint was met (Table); 39.8% vs 15.0% of pts receiving imetelstat vs placebo, respectively, achieved 8-wk TI. The rate of 8-wk TI was significantly higher with imetelstat vs placebo across subgroups, including RS negative pts. Median TI duration was significantly longer for imetelstat vs placebo, 51.6 vs 13.3 wks, P &lt; 0.001. Pts receiving imetelstat had significantly higher mean hemoglobin (P &lt; 0.001) and fewer transfusions (P = 0.042) over time than those on placebo. In 3 of 4 genes frequently mutated in MDS, VAF reduction was significantly greater in pts treated with imetelstat than placebo: SF3B1 (P &lt; 0.001), TET2 (P = 0.032), DNMT3A (P = 0.019) and ASXL1 (P = NS). SF3B1 VAF reduction correlated with longer TI duration, P &lt; 0.001. No new safety signals were identified. The most common Grade 3/4 AEs were thrombocytopenia and neutropenia, with similar rates of Grade ≥3 bleeding and infections on imetelstat and placebo. In pts treated with imetelstat, cytopenias were manageable, of short duration, and &gt;80% were reversible to Grade ≤2 within 4 wks. Conclusions: For this LR-MDS pt population, imetelstat demonstrated statistically significant and clinically meaningful efficacy with high 8- and 24-wk TI rates, prolonged TI duration and increased hemoglobin. VAF reduction and its correlation to clinical endpoints support imetelstat’s disease-modifying potential. Safety results were consistent with prior reported experience. Clinical trial information: NCT02598661 . [Table: see text]
Long-term outcomes of melanoma oligoprogressive metastases treated with radiotherapy combined with locoregional hyperthermia.
Authors: Aneta Borkowska, Mateusz Spalek, Pawel Teterycz, Piotr Rutkowski
Journal: Journal of Clinical Oncology (2023)

e21540 Background: Oligoprogression is a limited progression after a prior response to treatment. Oligoprogression remains a major clinical challenge in patients with metastatic melanoma (MM). Local therapy for progressing metastases may enable the continuation of effective systemic therapy. Methods: We identified 77 patients treated with radiotherapy combined with hyperthermia for oligoprogressive MM in a melanoma tertiary center between 2019 and 2022. Patients without any follow-up imaging after irradiation were excluded. We assessed local control (LC), and overall survival (OS). We estimated the correlation between BRAF status, size of the irradiated lesion, radiation dose, and LC. Survival analyses were performed using the Kaplan-Meier estimator, and Log-rank tests and were used for comparison between groups. The data cut-off was 31/Aug/2022. Results: The majority of patients (83%) had one oligoprogressive lesion. At the time of analysis, 59.5% of patients had stable disease, complete or partial response, and 40.5% of patients had progression, in the total response according to RECIST (Table). Most patients (78%) were irradiated during immunotherapy whereas 12% received concomitant BRAF and MEK inhibitors (Table). There were no severe toxicities of radiotherapy nor hyperthermia. The median follow-up was 18 (95%CI: 16-24) months(m). The 12 and 24m LC rates were: 83% (95%CI: 74-94) and 54% (95%CI: 40-73), respectively. The achieved LC rate was 88.3%. The 12 and 24m OS rates were: 87% and 72%, respectively. At the time of analysis, the median of OS and LC were not reached. BRAF status, size of the lesion, or radiation dose were not associated with LC. Conclusions: Preliminary data showed that patients with MM may benefit from radiotherapy combined with hyperthermia for oligoprogressive lesions during systemic treatment. This combination enables good local control of progressive metastases with minimal toxicity. This topic requires further investigation in prospective studies. [Table: see text]
Peripheral pre-existing cancer-antigen specific T-cell immunity as predictive biomarker for immunotherapy in NSCLC patients.
Authors: Anastasia Xagara, Sotirios P. Fortis, Maria Goulielmaki, Filippos Koinis, Evangelia Chantzara, Alexandros Kokkalis, Ioannis Samaras, Vasileios Papadopoulos, Vasileios Georgoulias, Constantin N Baxevanis, Athanasios Kotsakis
Journal: Journal of Clinical Oncology (2023)

e20504 Background: Pre-existing Tumor Antigen specific T-cells describe the endogenous adaptive immunity before any treatment that may represent a valuable novel predictive biomarker for ICI treatment. We investigate the potential value of pre-existing cancer-antigen specific CD8 + T-cells as a circulating predictive biomarker. Additionally, we analyze the major differences of known immune-cell phenotypes between Pre-existing positive (PreI+) and Pre-existing negative immunity (PreI - ) NSCLC patients. Here, we present the preliminary results of this study. Methods: Blood was collected from 24 patients with NSCLC, stage III PD-L1 + , after completion of radical chemoradiation, before initiation of maintenance durvalumab. PBMCs were isolated with Ficoll density gradient centrifugation from patients and 10 healthy donors (HD). PreI was calculated by detecting endogenous IFNg expressing cells with FACS after in-vivo co-cultures of PBMCs with mixes of hTERT, MAGEA1, NY-ESO-1 και Survivin cancer-associated antigens. Immunophenotyping was performed by multi-color flow cytometry using antibodies against CD3, CD4, CD8, CD45RA, CD45RO, CCR7, PD-1, PD-L1 for T-cells. Results: From 24 patients receiving Durvalumab, 10/24 (41.6%) had peptide specific T-cells (PreI + patients), 60% (6/10) had detectable peptide specific T cells for all (4/4) antigens tested. Survival analysis revealed better PFS in PreI + than PreI – patients (Log-rank = 0.06, median 333.5 and 185 days ) and better OS (p = 0.032, median not reached and 254 days). The levels of CD3CD4PD-1 were higher in patients compared to HD (p = 0.019) but there was not a difference between PreI + and PreI - patients (p = 0.25). PreI + patients had significantly higher numbers of CD3CD8PD-1 cells compared to PreI - (p = 0.024) but not CD3CD8PD-L1. Prei + patients had high numbers of Teff (CD3+CD8+CD45RA+CD45RO-CCR7) compared to both HD (p = 0.0039) and PreI - (p = 0.032). Conclusions: Pre-existing tumor antigen specific immunity before initiation of ICI in NSCLC patients could serve as a good predictive factor of response. The study is ongoing.
Clinicians’ experiences with patients with cancer or their families who endorse medical misinformation.
Authors: Amitabha Palmer, Colleen M. Gallagher
Journal: Journal of Clinical Oncology (2023)

11042 Background: Medical misinformation causes delays in cancer care, forgoing of treatment, economic harms, potentially toxic effects, and harmful medical interactions with standard curative treatments. Previous literature has examined patients’ traits and beliefs. However, effectively caring for patients with cancer who endorse medical misinformation also requires better understanding the experiences, competencies, and concerns of the clinicians who treat them. We conducted an IRB approved study of physicians and advanced practice providers at a large cancer center. Methods: We surveyed clinicians about following themes: i) prevalence of misinformation, ii) attitudes towards patients endorsing misinformation, iii) strategies and competence, iv) resources to help them successfully address patients. Results: 87 clinicians responded to the survey. The median response was 15% of patients endorse claims that are false or misleading about standard-of-care cancer treatments and 20% endorse claims that overstate the benefits or understate the risks of unconventional treatments. The most common misinformation concerned herbs and supplements. Clinicians ranked provides hope and poor medical literacy as the top reasons for why their patients endorse medical misinformation followed by distrust in conventional medicine, cultural factors, and religiosity. The primary attitude clinicians project to patients when they request unconventional treatments was Openness/Equanimity (75.6%), Curiosity (43.9%), Skepticism (18.3%), Disdain/Disappointment (0, 0.0%), Other (6.1%). The primary internal attitude clinicians experienced in these situations was Openness/Equanimity (25.6%), Skepticism (57.3%), Curiosity (40.2%), Disdain/Disappointment (22.0%), Other (6, 7.3%). When asked if they’d be open to a patient using a harmless unconventional treatment that had no evidence of therapeutic benefit, 17.1% said yes, 17.1% said no, and 65.9% said it depends. Correcting misinformation is difficult: 38.2% report success rates below 60% for correcting misinformation and 68.5% report success rates below 80%. Several factors contributed to low success: Only 26% said that they have enough time to adequately address patients who endorse misinformation. Moreover, 46.9% report insufficient resources, 65% claim insufficient training, and 51.3% claim insufficient institutional support. Conclusions: Many cancer care providers feel insufficiently trained and supported to address patients who endorse medical misinformation. Cancer care institutions must develop training and resources to help clinicians effectively address patients who endorse misinformation about their care.
Management and outcomes of advanced stage cardiac AL amyloidosis in the daratumumab era.
Authors: Ariana Feuvrier-Rivera, Anupama Deepa Kumar, Marcus Anthony Urey, Caitlin Costello
Journal: Journal of Clinical Oncology (2023)

e20058 Background: AL amyloidosis is plasma cell disorder involving irreversible deposition of amyloid fibrils, leading to end-organ damage. Treatment strategies include systemic therapy, autologous stem cell transplant (ASCT), and organ transplant. The ANDROMEDA trial established daratumumab (Dara) in combination with cyclophosphamide, bortezomib (Bor), and dexamethasone (CyBorD) as a new standard of care in newly diagnosed AL amyloidosis. Notably, only 2% of the trial population had stage IIIB cardiac disease by Mayo 2004 criteria. We present real world data of orthotopic heart transplantation (OHT) recipients with AL amyloidosis at our institution to understand the safety and outcomes of Dara use in the setting of advanced cardiac involvement. Methods: We performed a retrospective review of 9 patients at our institution who had received OHT since 2019 for AL amyloidosis. Demographics, disease details, treatment selection, response, and outcomes data were collected and described. Results: The cohort included 22% Black and 22% Hispanic patients, and the median age at diagnosis was 56. All patients had Revised Mayo stage 3 or 4 disease with advanced cardiac involvement requiring OHT. Patients had a median of 3 (2-4) suspected organs involved; none had symptomatic myeloma. Four patients received induction CyBorD; 2 achieved complete response (CR), 1 very good partial response (VGPR), and 1 partial response (PR) prior to OHT. Three of 4 received bridging therapy (Dara-Bor triplet or Bor alone) prior to ASCT, 2 due to inadequate response and 1 to maintain CR, and all achieved CR post-ASCT. Median time from OHT to ASCT was 13.5 months (range: 8-17), with bridging therapy starting at a median of 6 months post-OHT if received, with concomitant reduction in OHT immunosuppression. Five patients received DaraCyBorD induction: 2 achieved CR, 2 achieved VGPR, and 1 achieved PR prior to OHT. No patient who received DaraCyBorD received ASCT. Those not in CR received further therapy post-OHT. At the time of this analysis, 89% of patients remain in CR with 2 receiving ongoing therapy. All patients are alive with a median follow-up of 22 months (range: 11-35) since OHT without evidence for organ rejection. Conclusions: We demonstrate that the use of subcutaneous Dara is tolerable and effective in advanced stage cardiac AL amyloidosis, an underrepresented group in the literature. Patients who received DaraCyBorD followed by OHT without ASCT achieved similar outcomes to those who received CyBorD, OHT, and ASCT. The routine use of Dara may therefore negate the need for ASCT in this setting, given its favorable toxicity profile and reduced cost. [Table: see text]
Effectiveness of NEPA, an oral fixed-dose combination of netupitant and palonosetron in the prevention of chemotherapy induce nausea (CIN): A post-hoc analysis.
Authors: Amullya Pednekar, Sudeep Gupta, Ghanashyam Biswas, Chandrakanth MV, Palanki Satya Dattatreya, Boben Thomas, Sumant Gupta, Sagar B Bhagat, Saiprasad Patil, Hanmant V. Barkate
Journal: Journal of Clinical Oncology (2023)

e24140 Background: Despite widespread use of antiemetics, chemotherapy-induced nausea is still reported by upto 70% of adult patients receiving moderately emetogenic chemotherapy(MEC) or highly emetogenic chemotherapy (HEC) agents. Control of nausea remains an important, unmet need among cancer patients. The current evidence suggests that, overall, no significant nausea is reported by upto 75% of the patients with the aprepitant based regimens. Here, we present a post-hoc analysis of an observational study on NEPA (NEtupitant 300mg and PAlonosetron 0.50 mg) in preventing nausea in patients receiving HEC/MEC in a real-world setting in India. Methods: An open-label, single-arm, prospective study among chemonaive patients was conducted across six centers from April 2019 to December 2021 after approval from each institutional ethics committee (CTRI/2020/02/023586). A post-hoc analysis was carried out to assess the effectiveness of NEPA in preventing CIN in patients. The parameters assessed included severity of nausea using a visual analogue scale (VAS) [No significant nausea (includes no/mild nausea) &lt; 2.5cm on VAS scale, moderate nausea 2.5cm to 7.5cm, Severe nausea 7.5cm to 10cm], complete control (no nausea and complete response) and safety. Results: Of the 354 patients, 289 (81.64%) received the HEC regimen, and the remaining 65 (18.36%) received the MEC regimen. Anthracycline-Cyclophosphamide (36.16%) and FOLFOX (6.21%) were the most common HEC and MEC regimens, respectively. In the overall, acute, and delayed phases, no significant nausea was reported in 89.83%., 93.22% and 92.65% of the patients, respectively. Moderate and severe nausea was reported in 5.65%, and 1.13% of patients in the acute phase, 5.65%, and 1.69% in the delayed phase, and 8.19%, and 1.98% in the overall phase respectively. Among, those on HEC and MEC regimen, no significant nausea was reported in 93.42 % and 89.23 % respectively during the overall phase (Table 1). Complete control was achieved in 77.40% of patients in the overall phase, 82.77% in the acute phase, and 85.03% in the delayed phase. Adverse events were reported in 10 (3.4%) patients, with leg pain being the most common 3(0.8%). Conclusions: NEPA was found to be effective and well tolerated in preventing nausea in patients receiving HEC/MEC regimens, with almost 90% of patients reporting no significant nausea in real world Indian setting. Clinical trial information: CTRI/2020/02/023586 .[Table: see text]
Impact of SARS-COV2 infection on the clinical outcomes in patients with lung cancer.
Authors: Siri Chandana Swarna, Vaishali Deenadayalan, Rafaella Litvin, Mona Dasgupta, Junglee Kim, Shweta Gupta
Journal: Journal of Clinical Oncology (2023)

e20572 Background: The outbreak of 2019 Novel coronavirus disease (COVID-19) has led to various deleterious outcomes in cancer patients. Those with lung cancer would be more susceptible to increased morbidity and mortality. We aimed to study the outcomes of COVID infection in patients with lung cancer. Methods: Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database-2020 was queried to identify all admissions with COVID in patients with and without lung cancer. The groups were compared for socio-demographic differences, medical comorbidities, inpatient mortality, length of stay (LOS), and total hospital charges (THC). Secondary outcomes included a diagnosis of thrombocytopenia (TCP), Acute Respiratory Failure (ARF), sepsis, anemia, pancytopenia and shock. Statistics were performed using t-test, univariate and multinomial logistic regression. Results: A total 4,625 COVID admissions occurred in patients with lung cancer. Among them 71% (N = 3,288) were white, 17% (N = 805) were African American (AA) and 6.7% (N = 310) were Hispanic (HISP). Lung cancer patients had higher rates of smoking heart failure, CKD, CAD, COPD and anemia (p &lt; 0.01) and lower rates of DM and obesity (p &lt; 0.01). Lung cancer patients were more likely to have Medicare and less likely to have private insurance and were older (mean age 64.7 vs 71.9, p &lt; 0.01). On multivariate regression, after adjusting for confounders those with lung cancer had higher odds of all-cause mortality (aOR 1.41; 95% CI 1.18-1.70 ,p = &lt; 0.001). Among lung cancer patients, mean LOS was lower by 1 day (95% CI -1.4 to -0.4, p &lt; 0.001) and THC was also lower (-$16,672; 95% CI -22950 to -10393, p &lt; 0.001). Among the secondary outcomes, lung cancer patients had higher rates of pancytopenia (7.46% vs 1.59%, p &lt; 0.001), neutropenia (3.46% vs 0.68%, p &lt; 0.001) and venous thromboembolism (8.97% vs 4.29%, p = 0.006). Conclusions: COVID-19 infection led to increased mortality in lung cancer patients compared to those without lung cancer. This explains the overwhelming impact the pandemic left on lung cancer patients. The LOS and THC was decreased for lung cancer patients which may be explained by early death compared to non-lung cancer cohort. This study highlights the importance of decreasing the risk factors for COVID infection among lung cancer patients, including encouraging vaccination.
A pilot clinical study of oral irinotecan HCl (VAL-413) in patients with recurrent pediatric solid tumors.
Authors: Jeffrey A. Bacha, Dennis Brown, James I. Geller, Javier E. Oesterheld, Meghann McManus, Sarath Kanekal, Markos Leggas, Lorena Lopez, Neil Sankar, Noymi Yam, Lars M. Wagner
Journal: Journal of Clinical Oncology (2023)

TPS10073 Background: Intravenous irinotecan hydrochloride (IRN-IV) is approved for the treatment of adult colorectal cancer and also used off-label to treat a range of adult and pediatric tumors including recurrent Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, hepatoblastoma, Wilms tumor, gynecologic cancers, lung cancer and medulloblastoma. Previously, a regimen of IRN-IV administered as a 60-min i.v. infusion daily for 5 days, bi-weekly in combination with other agents such as temozolomide has been recommended use in treating children with solid tumors (Blaney. ClinCanRes, 2001). Protracted administration schedule of IRN-IV is inconvenient for patients, so oral regimens utilizing IRN-IV have been developed and implemented with favorable tumor response (Wagner. ClinSarcRes, 2015). Unfortunately, the palatability of the IRN-IV is poor, leading to reduced compliance especially in younger pediatric patients. Development of an advanced formulation to improve tolerability and patient compliance is an important unmet need. VAL-413 is a novel formulation developed to improve palatability of oral irinotecan. This pilot trial will examine the safety and tolerability of this novel formulation and assess pharmacokinetics compared to current oral regimen. Methods: Eligibility: Up to 20 patients ≥ 1 year of age or ≤ 30 years of age with recurrent pediatric solid tumors and adequate bone marrow, renal and liver function, for whom irinotecan therapy is a treatment option will be enrolled. Trial Design: Two different dose levels of VAL-413, 90mg/m2/day or 110mg/m2/day will be studied in combination with fixed-dose temozolomide using a standard 3 + 3 phase I design. In the event the starting dose of 90 mg/m2/day is not tolerable due to toxicity, a lower dose of 75 mg/m2/day may be implemented. Treatment: During the first cycle of treatment, each patient will receive 4 daily doses of VAL-413 and one daily dose of the intravenous preparation of irinotecan taken orally (IRN-IVPO). During all subsequent cycles, only VAL-413 will be given with temozolomide in 5-day courses administered every 21 days, as tolerated. Outcome Measures:Toxicity is assessed by NCI CCTCAEv5; tumor response is assessed by RECIST 1.1. A palatability survey instrument will assess palatability of VAL-413 vs. IRN-IVPO; comparative intra-patient pharmacokinetics of irinotecan and its metabolites will be assessed. This trial is ongoing (CT.gov: NCT04337177), with no DLT observed to date. Clinical trial information: NCT04337177 .